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Kaimen Rigor review

Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial.

Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R, Conti I, Cosaert J, Schwartz GK.

DOI: 10.1016/s0140-6736(16)30587-6
Record issued: 2026-08-03
Engine: 7.9.0
Exported: 2026-09-27

Prepared by Adcurare. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at adcurare.com/verify/9321b5be-f1d7-4b0f-a5e2-c6aee8aef656 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.25 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingKey resources not met−0.5★
ReportingData & code availability not met−0.5★
StatisticsPrinted percentage does not match its own count (capped) ×4−0.25★
ReportingEthical approvals partially met−0.25★
ReportingStatistical analysis partially met−0.25★

Model-reported confidence: moderateReviewer agreement: highEngine: 7.9.0Source: full text

Biggest issues

01Key resources not identified
highDisclosurereviewer-assessedFull detail
The investigational product (olaratumab) is described with dose and regimen but without a specific manufacturer catalog number or clone identifier. The active comparator (doxorubicin) is not identified by manufacturer. Statistical software is not identified. These are significant gaps in key resource reporting.
“Olaratumab is a recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that specifically binds PDGFRα, blocking PDGF-AA, -BB, and -CC binding and receptor activation.”
Introduction ¶3
02Data and code not shared
highDisclosurereviewer-assessedFull detail
No data availability statement is present. The study was registered at ClinicalTrials.gov (NCT01185964), but no data repository deposit or code sharing is mentioned. This is a critical omission for a clinical trial.
03Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
39% does not match the reported count 25/65
“neutropenia (25 [39%])”
Phase 2 adverse events
04Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
19% does not match the reported count 12/65
“vomiting (12 [19%])”
Phase 2 adverse events
05Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
79% does not match the reported count 51/65
“51 (79%)”
Phase 2 outcomes
06Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
19% does not match the reported count 12/65
“12 [19%]”
Phase 2 safety

2 further findings of this severity or below — every one is in the sections below, filed under its error type.

Findings by category

201ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 404DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

The paper describes a well-designed randomized phase 2 trial with a clear scientific rationale and generally adequate reporting. However, it has critical gaps in key resource identification, data availability, and statistical reporting (including two impossible confidence intervals that are likely typos), which reduce reproducibility and transparency.

All three independent reviewers (same model) agreed on all dimension statuses, with minor disagreements on sub-criteria. The paper was evaluated as a full-text clinical trial. The statistics verification covered only a subset of tests; the citation check flagged three references not found in registries. The two impossible confidence intervals were flagged by both the copyedit pass and integrity analysis.

Numerical inconsistencies

2 findings · worst medium

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed
Printed percentage does not match its own countRecomputed

Recomputed 7 tests: 7 consistent, 0 inconsistent; 7 via agent-written checks. 4 printed percentages that do not match their own count.

Numeric forensics— values impossible for the reported sample size

PERCENT
39% does not match the reported count 25/65
“neutropenia (25 [39%])”
Phase 2 adverse events
PERCENT
19% does not match the reported count 12/65
“vomiting (12 [19%])”
Phase 2 adverse events
PERCENT
79% does not match the reported count 51/65
“51 (79%)”
Phase 2 outcomes
PERCENT
19% does not match the reported count 12/65
“12 [19%]”
Phase 2 safety

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .061 · recomputed p = .063Reviewers 1, 3
Check p-value for progression-free survival from stratified HR and 95% CI.
How we recomputed it: pCI(0.672, 0.442, 1.021, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 3
Check p-value for overall survival from stratified HR and 95% CI.
How we recomputed it: pCI(0.46, 0.30, 0.71, 1)
CONSISTENTreported p = .342 · recomputed p = .314Reviewer 1
Check p-value for objective response rate (investigator assessment) using 2x2 table.
How we recomputed it: pChi2x2(12, 54, 8, 59)
CONSISTENTreported p = .074 · recomputed p = .064Reviewer 1
Check p-value for objective response rate (independent assessment) using 2x2 table.
How we recomputed it: pChi2x2(12, 54, 5, 62)
UNCOMPUTABLEreported p = .121 · recomputed p = .638Reviewer 1
Check p-value for independent review PFS from HR and CI.
How we recomputed it: pCI(0.67, 0.04, 1.12, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Overall survival HR = 0.46, 95% CI 0.30–0.71, p=0.0003. Compute p from CI.
How we recomputed it: pCI(0.46, 0.30, 0.71, 1)
CONSISTENTreported p = .061 · recomputed p = .063Reviewer 2
Progression-free survival HR = 0.672, 95% CI 0.442–1.021, p=0.0615. Compute p from CI.
How we recomputed it: pCI(0.672, 0.442, 1.021, 1)
CONSISTENTreported p = .342 · recomputed p = .314Reviewer 3
Check p-value for objective response rate (investigator) using chi-square from cell counts
How we recomputed it: pChi2x2(12, 54, 8, 59)

highinternal contradiction
The 95% confidence interval for the independent assessment objective response rate in the olaratumab+doxorubicin group is reported as '29·6–29·8', which is impossible for a proportion of 18.2% (the CI must contain the point estimate). This is likely a typographical error.
“The objective response rate for the independent assessment was 18·2% (95% CI, 29·6–29·8) with olaratumab+doxorubicin”
Results
mediuminternal contradiction
The 95% CI for the independent review PFS hazard ratio is reported as '0·04–1·12', which is extremely wide (lower bound near 0) and inconsistent with the investigator-assessed CI (0.442–1.021) for the same number of patients. This suggests a possible transcription error.
“0·670; 95% CI, 0·04–1·12; p=0·1208”
Results

Overstated conclusions

1 finding · worst low

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Conclusions only partially backed by the presented evidenceAssessed

12 major claims checked against the paper's own evidence: all adequately supported.

partialReviewers 1, 2
The combination of olaratumab plus doxorubicin improved both progression-free and overall survival compared with standard-of-care doxorubicin in patients with advanced soft tissue sarcoma.
The PFS improvement met the pre-specified alpha of 0.20 but not conventional 0.05, while the OS improvement is highly significant. The claim is partially supported because the PFS result is marginal.
Evidence: PFS: stratified HR 0.672, p=0.0615; OS: stratified HR 0.46, p=0.0003.
“The combination of olaratumab plus doxorubicin improved both progression-free and overall survival compared with the standard-of-care doxorubicin in patients with advanced soft tissue sarcoma.”
Abstract
partialReviewer 2
The inhibitory effect of olaratumab on tumour and stromal PDGFRα signaling may persist beyond the immediate treatment period.
The paper argues that the greater OS vs PFS benefit suggests a persistent effect, but this is speculative and not directly tested. It is a reasonable hypothesis based on the data.
Evidence: Discussion, paragraph 3: 'The magnitude of improvement observed in median overall survival ... was greater than that observed in progression-free survival ... suggesting that the inhibitory effect ... may persist beyond the immediate treatment period.'
“This finding suggests that the inhibitory effect of olaratumab on tumour and stromal PDGFRα signaling may persist beyond the immediate treatment period.”
Discussion ¶3
supportedReviewer 1
This study met its predefined primary endpoint for progression-free survival.
The primary endpoint used a two-sided alpha of 0.20, and the p-value of 0.0615 is below this threshold, so the claim is supported.
Evidence: PFS p=0.0615, pre-specified alpha 0.1999 after interim analysis.
“This study of olaratumab with doxorubicin in patients with advanced soft tissue sarcoma met its predefined primary endpoint for progression-free survival”
Abstract
supportedReviewer 1
Achieved a highly significant improvement of 11.8 months in median overall survival (P=0.0003; HR 0.46).
The reported OS difference is statistically significant at conventional levels, and the p-value is very low.
Evidence: Median OS 26.5 vs 14.7 months, HR 0.46, p=0.0003.
“achieved a highly significant improvement of 11·8 months in median overall survival (P=0·0003; HR 0·46)”
Abstract
supportedReviewers 1, 2
Our study is the first randomized study to show increased survival for patients with soft tissue sarcoma treated with an agent added to doxorubicin therapy.
The paper's literature search identified 19 prior randomized trials, none showing OS benefit, so this claim is supported by the presented evidence.
Evidence: Research in context panel and references.
“Our study is the first randomized study to show increased survival for patients with soft tissue sarcoma treated with an agent added to doxorubicin therapy.”
Panel: Research in context, Added value…
supportedReviewer 2
This study of olaratumab with doxorubicin in patients with advanced soft tissue sarcoma met its predefined primary endpoint for progression-free survival.
The primary endpoint was PFS at a two-sided α=0.20; the reported p=0.0615 is below this threshold, so the claim is supported.
Evidence: Results: Progression-free Survival; p=0.0615 < 0.1999.
“This study of olaratumab with doxorubicin in patients with advanced soft tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11·8 months in median overall survival (P=0·0003; HR 0·46).”
Abstract
supportedReviewer 2
The improvement in median overall survival was 11·8 months and is highly significant.
The paper reports median OS 26.5 vs 14.7 months, difference 11.8 months, p=0.0003, HR 0.46, directly supporting the claim.
Evidence: Results: Overall Survival; median OS values and p-value.
“achieved a highly significant improvement of 11·8 months in median overall survival (P=0·0003; HR 0·46).”
Abstract
supportedReviewer 3
The combination of olaratumab and doxorubicin met its predefined primary endpoint for progression-free survival.
The paper reports a PFS HR of 0.672 with a p-value of 0.0615, which met the pre-specified alpha of 0.1999.
Evidence: Results, Progression-free Survival: 'This improvement in favor of olaratumab+doxorubicin met the protocol-defined significance level of 0·1999 for final progression-free survival (stratified HR, 0·672; 95% CI, 0·442–1·021; p=0·0615).'
“This improvement in favor of olaratumab+doxorubicin met the protocol-defined significance level of 0·1999 for final progression-free survival (stratified HR, 0·672; 95% CI, 0·442–1·021; p=0·0615).”
Results
supportedReviewer 3
The combination achieved a statistically significant improvement in overall survival.
The OS HR is 0.46 with p=0.0003, which is highly significant.
Evidence: Results, Overall Survival: 'This difference of 11·8 months represented a statistically significant improvement in median overall survival (stratified HR, 0·46; 95% CI, 0·30–0·71; p=0·0003).'
This difference of 11·8 months represented a statistically significant improvement in median overall survival (stratified HR, 0·46; 95% CI, 0·30–0·71; p=0·0003).
Resultsreviewer’s wording
supportedReviewer 3
The safety profile of the combination is acceptable and does not increase serious toxicity.
The paper reports adverse events, including febrile neutropenia rates that are similar between groups, and notes that discontinuations were lower in the combination arm.
Evidence: Results, Adverse Events: 'The incidence of febrile neutropenia was similar in both groups: olaratumab+ doxorubicin (8 [13%]) vs doxorubicin (9 [14%]).' and 'The percentage of patients who discontinued treatment because of an adverse event was lower with olaratumab+doxorubicin than with doxorubicin (8 [13%] vs 12 [19%]).'
“The incidence of febrile neutropenia was similar in both groups: olaratumab+ doxorubicin (8 [13%]) vs doxorubicin (9 [14%]).”
Results
supportedReviewer 3
PDGFRα expression did not correlate with treatment outcome.
The interaction p-values for OS and PFS are not significant, supporting the claim.
Evidence: Results, PDGFRα Assessment and Outcomes Comparison Analysis: 'The interaction effect between PDGFRα expression (positive or negative) and treatment was not significant for either overall or progression-free survival (interaction p-values 0·3209 and 0·5924).'
“The interaction effect between PDGFRα expression (positive or negative) and treatment was not significant for either overall or progression-free survival (interaction p-values 0·3209 and 0·5924).”
Results
supportedReviewers 2, 3
This is the first randomized study to show increased survival with an agent added to doxorubicin in soft tissue sarcoma.
The paper cites a literature search showing no prior randomized trial with a survival advantage over doxorubicin alone.
Evidence: Panel: Research in context: 'We identified 19 randomized phase 2 or phase 3 clinical trials, none of which showed an overall survival advantage of single agent or combination therapy over doxorubicin alone.'
“We identified 19 randomized phase 2 or phase 3 clinical trials, none of which showed an overall survival advantage of single agent or combination therapy over doxorubicin alone.”
Panel: Research in context

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

4 findings · worst high

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data and code not sharedAssessed
Key resources not identifiedAssessed
Statistical reporting gaps (tests, assumptions, effect sizes)Assessed
Ethics/consent reporting incompleteAssessed

Eight Dimensions4 pass · 2 warn · 2 fail

The introduction cites prior work on the limited survival with doxorubicin and the lack of prior therapies improving overall survival. It acknowledges the unmet medical need and provides a logical rationale linking PDGF/PDGFR signaling to sarcoma biology. Limitations of prior research (e.g., no prior combination improving OS) are discussed. The study objectives follow directly from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific foundation by citing prior research on soft tissue sarcoma, doxorubicin, PDGF/PDGFR signaling, and preclinical data, and provides a logical rationale for the study hypothesis.

Evidence

“Soft tissue sarcoma is a rare and diverse group of solid tumours...Doxorubicin, either alone or in combination, remains a standard of care. However, survival for treated patients with metastatic disease is only 12 to 16 months, and the two-year survival rate is approximately 30%.”

Introduction ¶1

“Preclinical studies of olaratumab alone or in combination with doxorubicin have demonstrated antitumour activity in human sarcoma xenograft models.”

Introduction ¶3

“A detailed PubMed search was performed...none of which showed an overall survival advantage of single agent or combination therapy over doxorubicin alone.”

Panel: Research in context

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific foundation by citing relevant prior research on the poor prognosis of soft tissue sarcoma, the role of PDGF/PDGFR signaling, and the preclinical rationale for olaratumab.

Evidence

“However, survival for treated patients with metastatic disease is only 12 to 16 months, and the two-year survival rate is approximately 30%.”

Introduction ¶1

“Platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling plays a significant role in mesenchymal biology, including mesenchymal stem cell differentiation, growth, and angiogenesis.”

Introduction ¶2

“Preclinical studies of olaratumab alone or in combination with doxorubicin have demonstrated antitumour activity in human sarcoma xenograft models.”

Introduction ¶3

PASSReviewer 3· 95% conf

The paper establishes a clear scientific foundation by citing prior research on soft tissue sarcoma, the role of PDGF/PDGFR signaling, and preclinical data, and it provides a logical rationale for the study.

Evidence

“Soft tissue sarcoma is a rare and diverse group of solid tumours... Doxorubicin, either alone or in combination, remains a standard of care. However, survival for treated patients with metastatic disease is only 12 to 16 months, and the two-year survival rate is approximately 30%.”

Introduction ¶1

“Platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) signaling plays a significant role in mesenchymal biology... Preclinical studies of olaratumab alone or in combination with doxorubicin have demonstrated antitumour activity in human sarcoma xenograft models.”

Introduction ¶3

“Few, if any, novel therapies or chemotherapy combinations have been able to improve these poor outcomes”

Introduction ¶1

Randomization used minimization technique balancing key factors. Sample size and power are explicitly stated (130 patients, 80% power, two-sided α=0.20). Eligibility criteria are clearly defined. The intention-to-treat and safety populations are specified. Blinding is not fully described (open-label), but an independent blinded review of scans was conducted. The primary endpoint is progression-free survival, with a pre-specified interim analysis and alpha adjustment.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The study design is adequately described with a clear randomization method, power analysis, and inclusion/exclusion criteria. The open-label design is stated but without a rationale, and missing data handling is not detailed.

Evidence

“Randomisation was dynamic and used the minimization randomisation technique to balance patients by ECOG performance status (0–1 vs 2), histological tumour type (leiomyosarcoma vs synovial sarcoma vs other), immunohistochemical PDGFR expression (positive vs negative), and previous lines of treatment (0 vs ≥1 line of therapy)”

Methods

“We conducted an open-label phase 1b, randomised, phase 2 study of doxorubicin ± olaratumab in patients with unresectable/metastatic soft tissue sarcoma.”

Methods

“The phase 2 planned sample size was 130 patients, which assumed a 50% improvement in median progression-free survival (hazard ratio [HR], 0·67) for the olaratumab+doxorubicin group, a statistical power of 80%, and a two-sided significance level of 0·20.”

Statistical analysis

PASSReviewer 2· 95% conf

The study design is well-described with adequate randomization, power analysis, inclusion/exclusion criteria, and analysis populations. The open-label design is stated, and a blinded independent review was performed for sensitivity.

Evidence

Methods

Statistical analysis

“eligible patients were ≥18 years of age and had a histologically confirmed diagnosis of locally advanced or metastatic soft tissue sarcoma not previously treated with an anthracycline, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and available tumour tissue to determine PDGFRα expression by immunohistochemistry.”

Methods

PASSReviewer 3· 90% conf

The study design is adequately reported for a human RCT, with clear randomization, sample size calculation, and eligibility criteria, although the open-label design is stated without rationale.

Evidence

Methods

“The phase 2 planned sample size was 130 patients, which assumed a 50% improvement in median progression-free survival (hazard ratio [HR], 0.67) for the olaratumab+doxorubicin group, a statistical power of 80%, and a two-sided significance level of 0.20.”

Statistical analysis

“We conducted an open-label phase 1b, randomised, phase 2 study of doxorubicin ± olaratumab in patients with unresectable/metastatic soft tissue sarcoma.”

Abstract

Baseline characteristics table includes age, sex, race, ethnicity, ECOG performance status, and histological type. Age is reported with median and range. Health status is reported via ECOG. No justification needed for sex as both sexes are enrolled.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Sex, age, and demographics are reported, but weight is not reported. The study includes both sexes, and health status is reported via ECOG performance status.

Evidence

“Age—y: Median (range) 58·5 (22–85) [olaratumab+doxorubicin]; 58·0 (29–86) [doxorubicin]. Sex—no. (%): Male 26 (39·4%) and 33 (49·3%); Female 40 (60·6%) and 34 (50·7%).”

Table 1

“eligible patients were ≥18 years of age and had a histologically confirmed diagnosis...an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2”

Methods

absence[Methods and Results]

Weight is not reported.

PASSReviewer 2· 95% conf

Patient demographics, age, sex, race, ethnicity, and performance status are well-reported in Table 1. Health status is captured by ECOG. Both sexes are included, so sex justification is not applicable.

Evidence

“Sex—no. (%) Male 26 (39·4%) 33 (49·3%) | Female 40 (60·6%) 34 (50·7%) | Age—y Median (range) 58·5 (22–85) 58·0 (29–86)”

Table 1

“Race—no. (%) White 55 (83·3%) 60 (89·6%) | Black 6 (9·1%) 5 (7·5%) | Asian 2 (3·0%) 2 (3·0%)”

Table 1

“ECOG performance status—no. (%) 0–1 62 (93·9%) 63 (94·0%) | 2 4 (6·1%) 4 (6·0%)”

Table 1

PASSReviewer 3· 85% conf

Sex, age, and demographics are reported, but weight is not reported. The study includes both sexes, so sex justification is not applicable.

Evidence

“Sex—no. (%) Male 26 (39.4%) Female 40 (60.6%)”

Table 1

“Age—y Median (range) 58.5 (22–85)”

Table 1

“Race—no. (%) White 55 (83.3%) Black 6 (9.1%) Asian 2 (3.0%) ... ECOG performance status—no. (%) 0–1 62 (93.9%) 2 4 (6.1%)”

Table 1

The paper states that the protocol was approved by the institutional review board at each participating center, but does not name the specific IRB or provide a protocol number. Informed consent and compliance with the Declaration of Helsinki and ICH-GCP are reported.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementINADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Informed consent and regulatory compliance are adequately reported, but the IRB approval statement does not name the specific ethics committee, making it inadequate.

Evidence

“The protocol was approved by the institutional review board at each participating center.”

Methods

“All patients provided written informed consent to participate.”

Methods

“The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice.”

Methods

WARNReviewer 2· 85% conf

The paper states that the protocol was approved by the institutional review board at each participating center and that written informed consent was obtained. However, no specific IRB name or protocol number is provided, making the ethics statement somewhat vague.

Evidence

“The protocol was approved by the institutional review board at each participating center.”

Methods

“The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice.”

Methods

“All patients provided written informed consent to participate.”

Methods

WARNReviewer 3· 90% conf

The study reports written informed consent and regulatory compliance, but the IRB approval statement does not name the specific institutional review board, which is a minor reporting gap.

Evidence

“The protocol was approved by the institutional review board at each participating center.”

Methods

“All patients provided written informed consent to participate.”

Methods

“The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Guidelines for Good Clinical Practice.”

Methods

Olaratumab is described as a human anti-PDGFRα monoclonal antibody, but no clone or RRID is provided. Doxorubicin is named with dose only, no source. No software used for statistical analysis is mentioned. As a drug trial, reagents_identified is the key applicable criterion; it is inadequate. Software_tools_identified is not reported. Antibodies_identified is not applicable (therapeutic mAb scored under reagents). No other biological resources are used.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 85% conf

The investigational drugs (olaratumab and doxorubicin) are not identified with manufacturer or source, and statistical software is not identified, leading to a fail.

Evidence

“Olaratumab is a recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that specifically binds PDGFRα”

Introduction ¶3

“doxorubicin (75 mg/m2) on day 1 of each 21-day cycle”

Methods

absence[Methods, Statistical Analysis]

Statistical software is not identified.

FAILReviewer 2· 90% conf

The investigational product (olaratumab) is described with dose and regimen but without a specific manufacturer catalog number or clone identifier. The active comparator (doxorubicin) is not identified by manufacturer. Statistical software is not identified. These are significant gaps in key resource reporting.

Evidence

“Olaratumab is a recombinant human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that specifically binds PDGFRα, blocking PDGF-AA, -BB, and -CC binding and receptor activation.”

Introduction ¶3

“doxorubicin alone (75 mg/m 2 ) on day 1 of each 21-day cycle”

Methods

absence[Methods, Statistical Analysis]

No statistical software identified

FAILReviewer 3· 85% conf

The paper fails to identify several key resources: the antibody used for PDGFRα immunohistochemistry is not identified, the manufacturer/source of the investigational drugs is not stated, and no statistical software is mentioned.

Evidence

absence[Methods, PDGFRα Assessment]

The antibody used for PDGFRα IHC is not identified

absence[Methods, Patients and Methods]

Investigational drug source not stated

absence[Methods, Statistical Analysis]

Statistical software not identified

The primary analysis uses stratified hazard ratios, implying a Cox model, but the test is not explicitly named (e.g., 'stratified log-rank test'). For secondary endpoints, the method for comparing response rates is not stated. Exact p-values are given (e.g., p=0.0615, 0.0003, 0.3421). Effect sizes and CIs are reported. Kaplan-Meier curves and tables are presented. No software is mentioned. Assumptions such as proportional hazards are not discussed. Mathematical plausibility checks pass.

Sub-criteria

tests namedINADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Exact p-values and effect sizes with CIs are reported, and data presentation is adequate for a clinical trial. However, the specific statistical tests are not named, assumptions are not verified, and software is not identified.

Evidence

“stratified HR, 0·672; 95% CI, 0·442–1·021; p=0·0615”

Results

“The efficacy analyses were performed in the randomisation patient population (intention-to-treat population).”

Statistical analysis

absence[Methods, Statistical Analysis]

Statistical software is not identified.

WARNReviewer 2· 85% conf

Exact p-values and confidence intervals are reported, and data presentation is adequate. However, the specific statistical tests used are not named (e.g., log-rank test), test assumptions are not verified, and the statistical software is not identified. These omissions place the paper in the 'warn' category.

Evidence

“stratified HR, 0·672; 95% CI, 0·442–1·021; p=0·0615”

Results

“stratified HR, 0·46; 95% CI, 0·30–0·71; p=0·0003”

Results

absence[Methods, Statistical Analysis]

No statistical software identified

WARNReviewer 3· 85% conf

Exact p-values, effect sizes with confidence intervals, and data presentation are adequate, but statistical tests are not explicitly named in the methods, assumptions are not verified, and software is not identified.

Evidence

“p=0.0615”

Results

“stratified HR, 0.672; 95% CI, 0.442–1.021”

Results

absence[Methods, Statistical Analysis]

Statistical tests are not explicitly named in methods

The paper does not include a data availability statement. The only link is to the protocol at the Lancet website. No individual patient data or aggregated data are deposited in a public repository. No custom code is shared. While the trial is registered, this does not satisfy data availability requirements.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

No data availability statement is present; the only statement is about the protocol being available. Data are not deposited in a repository, and no code is shared.

Evidence

absence[Entire paper]

No data availability statement.

“The protocol is available at http://www.thelancet.com/.”

Methods

FAILReviewer 2· 95% conf

No data availability statement is present. The study was registered at ClinicalTrials.gov (NCT01185964), but no data repository deposit or code sharing is mentioned. This is a critical omission for a clinical trial.

Evidence

absence[Entire paper]

No data availability statement

absence[Entire paper]

No repository deposit

absence[Entire paper]

No code sharing

FAILReviewer 3· 95% conf

The paper does not include a data availability statement, and no data are deposited in a repository. No code sharing is applicable.

Evidence

absence[Entire manuscript]

No data availability statement is present

Methods are complete enough for replication. The trial is registered at ClinicalTrials.gov (NCT01185964). All pre-specified outcomes (PFS, OS, ORR, safety) are reported. Limitations are discussed, including the PDGFRα assay issue and potential confounding. Conclusions are proportional to the evidence. Funding and conflicts are fully disclosed. No reporting guideline (e.g., CONSORT) is referenced, but this is a minor omission.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The paper is generally well-reported: methods are detailed, trial registration is provided, all key outcomes are reported, conclusions are proportional, and funding/COI are disclosed. However, a reporting guideline is not referenced, and limitations are discussed only implicitly.

Evidence

“This study was registered with ClinicalTrials.gov (http://ClinicalTrials.gov), number NCT01185964.”

Methods ¶1

“Funding Eli Lilly and Company.”

Abstract

absence[Methods]

No reporting guideline is referenced.

PASSReviewer 2· 90% conf

The paper provides detailed methods, reports all outcomes, discusses limitations, and includes funding and conflict-of-interest statements. The trial is registered. The only omission is a reference to a reporting guideline (e.g., CONSORT).

Evidence

“This study was registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , number NCT01185964 .”

Abstract

“While tumour PDGFRα expression alone did not correlate with outcome, tumour samples available for study were a heterogeneous mixture of archival primary and metastatic tumours.”

Discussion ¶4

“This study was funded by Eli Lilly and Company. ... AQ, AS, DMC, RI, IC are employees of and stockholders in Eli Lilly and Company.”

Ethics

PASSReviewer 3· 90% conf

The paper provides comprehensive reporting with trial registration, funding disclosure, and discussion of limitations, though a reporting guideline is not mentioned.

Evidence

“This study was registered with ClinicalTrials.gov (http://ClinicalTrials.gov), number NCT01185964.”

Abstract

“This study was funded by Eli Lilly and Company.”

End of manuscript

paraphrase[Discussion]

“The authors discuss the open-label design, small sample size, and potential confounding factors.”

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

NCT01185964

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 22 references: 19 verified — 3 unresolved.

INCOMPLETE
PICASSO 3: a phase 3 international randomized double blind placebo-controlled study of doxorubicin plus palifosfamide vs. doxorubicin plus placebo for patients in first-line for metastatic soft tissue sarcoma
No DOI in the reference list, and this analysis predates DOI-first auditing. Shown for review - not a fabrication signal.
INCOMPLETE
Enhanced antitumour activity of anti-platelet derived growth factor receptor alpha antibody, IMC-3G3, in combination with doxorubicin against a human soft-tissue sarcoma xenograft model
No DOI in the reference list, and this analysis predates DOI-first auditing. Shown for review - not a fabrication signal.
INCOMPLETE
Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial
No DOI in the reference list, and this analysis predates DOI-first auditing. Shown for review - not a fabrication signal.

2 data/code links checked; 1 live.

datahttp://ClinicalTrials.govLIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttp://www.thelancet.com/UNVERIFIEDHTTP 403
Liveness indeterminate — content not checked.

Copyediting

1 finding · worst low

Wording, consistency and formatting errors that need correcting before submission.

Wording or formatting errors that need correctingAssessed

11 copyedit issues flagged (2 major): mostly consistency, clarity, typo.

MAJORconsistencyResults, Objective Response Rate
“18·2% (95% CI, 29·6–29·8)”
→ 18·2% (95% CI, 9·8–29·6) or similar plausible range
The confidence interval 29.6–29.8 is implausible for a proportion of 18.2%; likely a typo.
MAJORconsistencyResults, Progression-free Survival, independent assessment
“0·670; 95% CI, 0·04–1·12”
→ 0·670; 95% CI, 0·40–1·12 or similar
The lower bound of 0.04 is suspiciously low for an HR of 0.67 with 133 patients; likely a typo.
MINORtypoResults, Adverse Events paragraph
“aspirational pneumonia”
→ aspiration pneumonia
Medical term is 'aspiration pneumonia'.
MINORclarityTable 4 footnote
“* No. of patients (%) for musculoskeletal pain was 5 (7.8) for grade ≥3 in the olaratumab+doxorubicin group. ** No. of patients (%) for musculoskeletal pain was 1 (1.5) for grade ≥3 in the doxorubicin group.”
→ Integrate the grade ≥3 data into the main table or clarify why they are footnoted.
The table has missing cells for grade 3/≥4 for musculoskeletal pain; footnotes provide the information but inconsistently.
MINORconsistencyTable 4, footnote c
“Consolidated term comprising the following preferred terms: fatigue, asthenia.”
→ Ensure consistent formatting of 'asthenia' (used elsewhere) vs. 'asthenia'.
No actual error found; minor.
MINORotherResults, line 'Neutropenia ,' in Table 4
“Neutropenia ,”
→ Remove extra space before comma.
Minor typographical issue.
MINORclarityResults, line 'Febrile neutropenia of grade ≥3 was similar in both groups (olaratumab plus doxorubicin 8 (13%) vs doxorubicin 9 (14%).'
“Febrile neutropenia of grade ≥3 was similar in both groups (olaratumab plus doxorubicin 8 (13%) vs doxorubicin 9 (14%).”
→ Consider adding 'and' for clarity: '8 (13%) and 9 (14%)'.
Minor readability.
MINORtypoResults, Adverse Events
“aspirational pneumonia”
→ aspiration pneumonia
Likely a typo for 'aspiration pneumonia'.
MINORpunctuationTable 4
“Neutropenia ,”
→ Neutropenia
Extra comma after 'Neutropenia'.
MINORconsistencyAbstract, Results
“Adverse events more frequent with olaratumab+doxorubicin vs doxorubicin alone included neutropenia (38 [59%] vs 25 [39%])”
→ Adverse events more frequent with olaratumab+doxorubicin vs. doxorubicin alone included neutropenia (38 [59%] vs. 25 [39%])
Missing space before 'vs' and period after 'vs' for consistency.
MINORclarityResults, Objective Response Rate
“The objective response rate for the independent assessment was 18·2% (95% CI, 29·6–29·8) with olaratumab+doxorubicin”
→ The objective response rate for the independent assessment was 18·2% (95% CI, 9·8–29·6) with olaratumab+doxorubicin
The confidence interval for the independent assessment appears to be a copy-paste error; it should match the earlier CI or be corrected.

Kaimen Rigor Action ItemsFinal pass before journal submission

As a published paper, this work shows moderate robustness: the primary conclusions are supported by the reported data, but the missing resource identifiers, absent data availability statement, and the presence of impossible confidence intervals (likely typos) undermine transparency and reproducibility. Readers should treat the reported confidence intervals for the independent assessment ORR and PFS HR as unreliable pending correction. An erratum should be issued to correct the CI typos, and a data availability statement should be added to the online version.

1.
CRITICALstatistics
Correct the impossible confidence interval for the independent assessment objective response rate (18.2% with 95% CI 29.6–29.8) in the Results section; the correct CI should contain the point estimate (e.g., 9.8–29.6).
This is a mathematical impossibility that undermines the credibility of the reported results and requires an erratum.
2.
CRITICALstatistics
Correct the suspiciously wide confidence interval for the independent review progression-free survival hazard ratio (0.670 with 95% CI 0.04–1.12) in the Results section; the lower bound 0.04 is implausibly low for the given sample size and point estimate.
This is likely a transcription error; the correct CI should be verified and reported accurately.
3.
CRITICALdata code
Add a data availability statement to the published article (e.g., in the end matter or via an online addendum) specifying whether and how individual patient data can be accessed.
Clinical trials are expected to provide data availability statements; the current absence is a major transparency gap.
4.
HIGHrigor
Identify the manufacturer/source of olaratumab and doxorubicin, and the clone/vendor of the antibody used for PDGFRα immunohistochemistry, in the Methods section.
Reproducibility requires knowing the sources of key reagents; this is a core resource identification gap.
5.
HIGHstatistics
Name the statistical software used (e.g., SAS version 9.4) in the Statistical Analysis section.
Software identification is standard for reproducibility.
6.
HIGHstatistics
Explicitly name the statistical tests used for each analysis (e.g., 'stratified log-rank test' for PFS) in the Methods section.
The current description is vague and does not allow verification of the test's appropriateness.
7.
HIGHstatistics
State whether the proportional hazards assumption was verified for the Cox models used in the primary analysis.
Without verification, the validity of the hazard ratios and p-values is uncertain.
8.
HIGHreporting
Add a reference to the CONSORT reporting guideline and provide a completed CONSORT checklist as supplementary material.
Most clinical trial journals require this; its absence is a transparency gap.
9.
HIGHother
Verify the three references that were not found in registries (PICASSO 3, anti-PDGFRα antibody study, sequential treatment assignment paper) and update or correct them as needed.
Unresolved references may be fabricated or mis-cited, undermining the paper's credibility.
10.
MEDIUMethics
Name the specific institutional review board(s) that approved the study and provide a protocol number in the Study Oversight section.
A generic IRB statement is insufficient for full ethical transparency.
11.
MEDIUMreporting
Provide a rationale for the open-label design in the Methods or Discussion sections.
Acknowledging potential biases from lack of blinding strengthens the paper's credibility.
12.
MEDIUMcopyedit
Fix the typo 'aspirational pneumonia' to 'aspiration pneumonia' in the Adverse Events section.
This is a medical terminology error that could confuse readers.
13.
LOWreporting
Report weight or body mass index in the baseline characteristics table (Table 1) as it is relevant for chemotherapy dosing.
While not standard for all cancer trials, it would improve completeness.
14.
LOWcopyedit
Remove the extra space before the comma in 'Neutropenia ,' in Table 4.
Minor typographical cleanup.

Full text (43,081 chars)Analyzed: Jul 28, 2026

RigorReviewer 1

RigorReviewer 2

RigorReviewer 3

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Kaimen Rigor grades the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolates the paper’s major claims and checks its own evidence backs them, and flags integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

This Kaimen Rigor review uses Kaimen Rigor trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial.

DOI

10.1016/s0140-6736(16)30587-6

Record issued

2026-08-03

Engine

7.9.0

Exported

2026-09-27